1-Piperazinecarboxylic acid, ethyl ester → HCID 18753464, compound

HRID 1838557Notes

Reaction equation

HRID 1838557 reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=3[F:23])=[N:10][CH:11]=[N:12]2)=[CH:7][C:6]=1[O:24][CH3:25].[CH2:26]([O:28][C:29]([N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1)=[O:30])[CH3:27]>O>[ClH:22].[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([NH:15][C:9]2[C:8]3[C:13](=[CH:14][C:5]([O:4][CH2:3][CH2:2][N:34]4[CH2:33][CH2:32][N:31]([C:29]([O:28][CH2:26][CH3:27])=[O:30])[CH2:36][CH2:35]4)=[C:6]([O:24][CH3:25])[CH:7]=3)[N:12]=[CH:11][N:10]=2)=[C:17]([F:23])[CH:18]=1

Participants

4

Reactant 2

HCID 84311-Piperazinecarboxylic acid, ethyl esterHCID 187534227-(2-Bromoethoxy)-4-(4-chloro-2-fluoroanilino)6-methoxyquinazoline

Product 1

HCID 18753464HCID 18753464, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 7-(2-bromoethoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (130 mg, 0.36 mmol), (prepared as described for the starting material in Example 62), in 1-ethoxycarbonylpiperazine (1.5 ml) was stirred and heated at 100° C. for 2 hours. The mixture was allowed to cool, diluted with water and extracted with ethyl acetate (3×25 ml). The extracts were combined, washed with water (×2) and then brine, and dried (MgSO4). The solvent was removed by evaporation and the residue was dissolved in acetone and 1M ethereal hydrogen chloride (2 ml) was added. The resulting precipitate was collected by filtration and then purified by column chromatography eluting with methylene chloride/methanol/aqueous ammonia (94/5/1). The purified product was dissolved in acetone and 1M ethereal hydrogen chloride (2 ml) was added. The resulting precipitate was collected by filtration, washed with ether and dried to give 4-(4chloro-2-fluoroanilino)-7-(2-(4-ethoxycarbonylpiperazin-1-yl)ethoxy)-6-methoxyquinazoline hydrochloride (85 mg, 46%).

Workup

  1. temperatureto cool
  2. extractionextracted with ethyl acetate (3×25 ml)
  3. washwashed with water (×2)
  4. dry with materialbrine, and dried (MgSO4)
  5. customThe solvent was removed by evaporation
  6. dissolutionthe residue was dissolved in acetone
  7. addition1M ethereal hydrogen chloride (2 ml) was added
  8. filtrationThe resulting precipitate was collected by filtration
  9. custompurified by column chromatography
  10. washeluting with methylene chloride/methanol/aqueous ammonia (94/5/1)
  11. dissolutionThe purified product was dissolved in acetone
  12. addition1M ethereal hydrogen chloride (2 ml) was added
  13. filtrationThe resulting precipitate was collected by filtration
  14. washwashed with ether
  15. customdried

Sources & evidence

ORD record
ord-6b23bb3b360e4791b0b1eb2edd630df7
Source dataset
uspto-grants-2004_01
Patent number
US06673803B2

Reaction notes

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